Dialysis is the most commonly applied physical principle to address the build-up of urea in the blood of patients with kidney failure. Dialysis membranes employed in dialysis treatment are typically only selective toward molecular weight and not toward other properties such as charge. As such, urea, ions and other small molecules can move across the dialysis membrane unimpeded from a higher concentration to a lower concentration, thereby lowering the concentration of such species in the patient's blood. Waste species entering the dialysate and impurities are removed by a sorbent cartridge before the dialysate is reused for dialysis.
In order for spent dialysate to be reused, accumulated waste products and impurities must be removed from the spent dialysate, and the composition and pH of the regenerated dialysate must be regulated for physiological compatibility. Devices that regenerate spent dialysis fluid for reuse are primarily directed toward the removal of urea, ammonium ions, uric acid, creatinine, and phosphate via various sorbents. For example, the Recirculating Dialysate System (“REDY system”), which was introduced in the 1970s, employs a sorbent cartridge through which spent dialysate is recirculated and regenerated. However, the regenerated dialysate produced by REDY systems is subject to variations in pH and sodium requiring ongoing adjustment.
Moreover, traditional dialysis systems employing sorbent technology, such as the REDY system usually employ low-flux dialyzers and adjust dialysate pressure to achieve net patient fluid removal. The UF coefficient of a dialyzer specifies the rate of filtration through the dialyzer due to pressure differences across the dialyzer membrane, typically called the trans-membrane pressure. The trans-membrane pressure is calculated by the formula TMP=((Blood Inlet Pressure+Blood Outlet Pressure)/2)−((Dialysate Inlet Pressure+Dialysate Outlet Pressure)/2). This formula is usually shortened to TMP=Venous Return Pressure−Dialysate Pressure. Low flux hemodialyzers have a UF coefficient of less than 8 ml of water flux per hour per mmHg of trans-membrane pressure. To illustrate fluid removal with the traditional sorbent system, a typical low flux dialyzer could have a UF coefficient of 4 mL/hr/mmHg. To calculate the pressure necessary to achieve the rate of fluid removal, the desired hourly fluid removal is divided by the dialyzer UF coefficient. For example, an hourly rate of 0.5 L/hr yields a required trans-membrane pressure (TMP) of 125 mmHg if the UF coefficient is 4 mL/hr/ mmHg. 125 mmHg is the trans-membrane pressure required to remove fluid at a rate of 0.5 L per hour. The venous pressure is a function of the blood flow rate and the blood return restriction (needle and access). As the Venous Return Pressure cannot be set, to control the fluid removal rate it is necessary calculate the required dialysate pressure. The operator calculates dialysate pressure via the formula Dialysate Pressure=Venous Pressure−TMP, if the venous return pressure were 75 mmHg, (DP=75−125=−50 mmHg). In this example the user must adjust the dialysate pressure to −50 mmHg to achieve the TMP of 125 mmHg. The venous pressure fluctuates during treatment so the operator must adjust the dialysate pressure on a regular basis, which is not suitable for a non-medical professional or a home patient. With high-flux dialyzers, pressure alone is not accurate enough to control ultrafiltration because fluid moves more freely across the dialyzer membrane. To control ultrafiltration in conventional hemodialysis using high-flux dialyzers, balancing chambers, flow sensors or other methods to balance flow to and from the dialyzer are employed. In CRRT (continuous blood purification machine) equipment, pumps controlled by precise scales are required to control the flow to and from the dialyzer very accurately.
Further development of dialysate recirculating techniques has resulted in systems that employ a variety of sorbent media, including activated carbon, urease, and zirconium-, aluminum-, and magnesium-based compounds. One of the problems associated with sorbent regeneration of spent dialysate is the buildup of sodium ions released as a byproduct of the absorption process, which operates by cation exchange. Further, electrolytes such as calcium, magnesium, and potassium are removed from spent dialysate by sorbent and deionization media and must be added back to the dialysate prior to reuse, which degrades the useful lifetime of cation exchange materials used as sorbent media.
Moreover, the sorbent cartridge is usually formed of expensive materials such as zirconium-based materials. Urea, the main metabolic waste product found in the blood, is a neutral, water-miscible compound making urea difficult to remove from the dialysate through absorption of large quantities. Urea is converted by an enzyme present in the sorbent cartridge to convert urea to ammonia and carbon dioxide. At the slightly basic pH of the dialysate, ammonia is present as positively-charged ammonium ions that are more easily absorbed by ion exchange materials. However, the use of ion exchange materials to remove urea/ammonium also removes other electrolytes that are present in the dialysate to maintain physiological compatibility, including Mg2+, Ca2+ and K+. A large portion of the cation absorption capacity, and hence ammonium absorption capability, provided by the zirconium materials of the sorbent cartridge is consumed by the absorption of Mg2+, Ca2+ and K+. There is a clear need for preserving ammonium absorption capability.
U.S. Pat. No. 3,669,878 Marantz et al. describes sorbent removal of urea and ammonium ions from spent dialysate via urease, ammonium carbonate, and zirconium phosphate, U.S. Pat. No. 3,669,880 Marantz et al. describes directing a controlled volume of dialysate through zirconium phosphate, activated carbon, and hydrated zirconium oxide columns, U.S. Pat. No. 3,850,835 Marantz et al. describes production of a zirconium hydrous oxide ion exchange media, and U.S. Pat. No. 3,989,622 Marantz et al. describes absorption of urease on aluminum oxide and magnesium silicate media to convert liquid urea to ammonium carbonate. U.S. Pat. No. 4,581,141 Ash describes removal of uremic waste species from dialysate via a calcium-based cation exchanger, urease, and aliphatic carboxylic acid resin. U.S. Pat. No. 4,826,663 Alberti et al. describes a method of preparing a zirconium phosphate ion exchanger. U.S. Pat. No. 6,627,164 Wong describes production of sodium zirconium carbonate for ion exchange in renal dialysis, and U.S. Pat. No. 7,566,432 Wong describes production of zirconium phosphate particles for ion exchange in regenerative dialysis. U.S. Pat. No. 6,818,196 Wong, U.S. Pat. No. 7,736,507 Wong, U.S. Application Publication 2002/0112609 Wong, U.S. Application Publication 2010/0078387 Wong, and U.S. Application Publication 2010/00784330 Wong, describe cartridges for purification of dialysis solutions using sodium zirconium carbonate. U.S. Pat. No. 6,878,283 Thompson, U.S. Pat. No. 7,776,210 Rosenbaum et al., U.S. Application Publication 2010/0326911 Rosenbaum et al., U.S. Application Publication 2010/0078381 Merchant, U.S. Application Publication 2009/0127193 Updyke et al. and U.S. Application Publication 2011/0017665 Updyke et al. describe filter cartridges having a plurality of types of filter media including zirconium compounds, urease, and alumina for dialysis systems. WO 2009/157877 A1 describes a urease material having urease immobilized on a substrate intermixed with a cation exchange material or zirconium phosphate material to improve workability for the reduction of clogging and to improve absorption of ammonium ions generated by the urease.
With regard to the management of impurities in regenerated dialysate, U.S. Pat. No. 4,460,555 Thompson and U.S. Pat. No. 4,650,587 Polak et al. describes magnesium phosphate media for removal of ammonia from aqueous solutions. U.S. Application Publication 2009/0282980 Gura et al. describes degassing devices for use in dialysate systems having urease media.
There is a need for unsupervised operation in mobile or home-based systems by a patient that maximizes the safety of the system to levels beyond those required for operation in a clinical setting. There is also a need to reduce the cost of consumable materials, such as the sorbent cartridge, that are covered by a single patient utilizing a mobile or at home-based system. Further, there remains a need for patient-friendly wearable and/or portable dialysis systems (collectively also referred to as mobile-based systems) that are capable of operating on a small volume of dialysate and suitable for daily continuous or short-term dialysis.